Phytomedicine最新文献

{"title":"Pectin-coated Malvidin-3-O-galactoside attenuates silica-induced pulmonary fibrosis by promoting mitochondrial autophagy and inhibiting cell apoptosis.","authors":"Yihan Yang, Chuang Ma, Yining Wang, Jinlong Tian, Bin Li, Jin Zhao","doi":"10.1016/j.phymed.2025.156566","DOIUrl":"10.1016/j.phymed.2025.156566","url":null,"abstract":"<p><strong>Background: </strong>Blueberries are a rich source of anthocyanins, which have been established to have multiple beneficial properties. However, the structure of anthocyanin monomers is unstable and their bioavailability is low. To date, whereas functional studies on anthocyanins have focused mainly on the effects of their monomers on liver and kidney, few have examined the interventional effects on pulmonary fibrosis.</p><p><strong>Purpose: </strong>In this study, we combined malvidin-3-O-galactoside (M3G)¹ derived from blueberries with pectin (PEC)² to form an anthocyanin-pectin complex (M3G-PEC),³ the anti-fibrotic effects of which were examined by administering to mice with modeled pulmonary fibrosis induced by silica particles (SP).⁴ METHODS: To evaluate the therapeutic effects and mechanisms of action of M3G-PEC with respect to the progression of pulmonary fibrosis, we measured autophagy- and apoptosis-related indices in C57BL/6 mice and mouse alveolar macrophage cell line (MH-S).⁵ RESULTS: The results of in vivo and in vitro studies revealed that M3G-PEC can alleviate the degree of pulmonary fibrosis, enhances the expression of Microtubule-associated protein light chain 3 (LC3),⁶ PTEN-inducible putative kinase 1 (PINK1),⁷ Parkin and B-cell lymphoma-2 (BCL-2),⁸ and causes the down-regulation of Caspase-3, P62, p-mammalian target of rapamyein (p-mTOR),⁹ phosphorylated protein kinase B (p-Akt)¹⁰ and Bax. And then, M3G-PEC contributes to maintaining a steady mitochondrial membrane potential and reduces the release of cytochrome c (Cyt-C)¹¹ in cells.</p><p><strong>Conclusion: </strong>Collectively, these findings indicate that M3G-PEC can preserve the bioactivity of anthocyanins and effectively enhance their bioavailability. Moreover, by regulating the BECN-1/Akt/mTOR pathway, M3G-PEC can influence the progression of silica-induced pulmonary fibrosis.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"139 ","pages":"156566"},"PeriodicalIF":6.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to \"B. glomerulata promotes neuroprotection against ischemic stroke by inhibiting apoptosis through the activation of PI3K/AKT/mTOR pathway\" [Phytomedicine, 2024, 132:155817].","authors":"","doi":"10.1016/j.phymed.2025.156636","DOIUrl":"https://doi.org/10.1016/j.phymed.2025.156636","url":null,"abstract":"","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":" ","pages":"156636"},"PeriodicalIF":6.7,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143711070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diosmin alleviates colitis by inhibiting PANoptosis of intestinal epithelial cells and regulating gut microbiota and metabolites","authors":"Cheng Tan ,&nbsp;Zixuan Xiang ,&nbsp;Shuo Wang ,&nbsp;Haodong He ,&nbsp;Xiangyun Li ,&nbsp;Miao Xu ,&nbsp;Xingzhou Guo ,&nbsp;Yu Pu ,&nbsp;Junhai Zhen ,&nbsp;Weiguo Dong","doi":"10.1016/j.phymed.2025.156671","DOIUrl":"10.1016/j.phymed.2025.156671","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Inflammatory bowel disease (IBD), particularly ulcerative colitis (UC), is a chronic inflammatory disorder characterized by an unclear etiology, often linked to gut microbiota dysbiosis and immune dysregulation. Existing UC therapies are constrained by suboptimal efficacy and adverse effects, underscoring the necessity for novel therapeutic strategies. Diosmin (DIO), a naturally occurring flavonoid, has demonstrated anti-inflammatory and antioxidant potential, yet its precise mechanisms and therapeutic role in colitis remain poorly understood.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Purpose&lt;/h3&gt;&lt;div&gt;This study aimed to investigate the therapeutic efficacy and mechanistic underpinnings of DIO in dextran sulfate sodium (DSS)-induced colitis, with a focus on its effects on intestinal epithelial cell PANoptosis, gut microbiota composition, fecal metabolites, and an in vitro inflammatory model using human colonic epithelial cells.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Study Design&lt;/h3&gt;&lt;div&gt;A controlled experimental design was employed, utilizing a DSS-induced murine colitis model and an LPS-induced inflammatory model in human colonic epithelial cells (NCM460). Mice were allocated into four groups: normal control, DSS-induced colitis, low-dose DIO (DIO-L, 100 mg/kg), and high-dose DIO (DIO-H, 200 mg/kg). In vitro experiments involved treating NCM460 cells with varying DIO concentrations post-LPS stimulation to assess its impact on inflammation and epithelial barrier integrity.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;Mice were administered DIO orally at 100 mg/kg or 200 mg/kg daily. Therapeutic outcomes were evaluated through body weight monitoring, Disease Activity Index (DAI) scoring, and histopathological examination. Gut microbiota composition was analyzed via 16S rRNA sequencing, while untargeted metabolomics was employed to profile fecal metabolites. Data integration was performed using O2PLS and WGCNA to identify microbiota-metabolite correlations. In vitro, immunofluorescence staining and Western blotting were utilized to evaluate the expression of tight junction proteins (ZO-1, E-cadherin, and Occludin).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;DIO administration significantly ameliorated colitis symptoms in mice, as evidenced by attenuated weight loss, reduced DAI scores, and preserved colon length. Histopathological analysis confirmed diminished inflammation and tissue damage in DIO-treated groups. Mechanistically, DIO suppressed the expression of PANoptosis-associated genes and proteins, including ZBP1 and Caspase-1, while maintaining epithelial barrier integrity in vitro. Furthermore, DIO modulated gut microbiota composition, promoting beneficial taxa such as Ruminococcus and reducing pathogenic Proteobacteria. Metabolomic profiling revealed alterations in key metabolic pathways, including flavonoid and steroid hormone biosynthesis, which correlated with microbiota changes.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;DIO effectively mitigates DSS-induced colit","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"141 ","pages":"Article 156671"},"PeriodicalIF":6.7,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143697734","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modified huangfeng decoction alleviates diabetic nephropathy by activating autophagy and regulating the gut microbiota","authors":"Yinhua Ni ,&nbsp;Wenlong Yang ,&nbsp;Sisi Wang ,&nbsp;Yuxiang Pan ,&nbsp;Haimei Du ,&nbsp;Liujie Zheng ,&nbsp;Cheguo Cai ,&nbsp;Zhengwei Fu ,&nbsp;Qiang He ,&nbsp;Juan Jin ,&nbsp;Peipei Zhang","doi":"10.1016/j.phymed.2025.156677","DOIUrl":"10.1016/j.phymed.2025.156677","url":null,"abstract":"<div><h3>Background</h3><div>Diabetic nephropathy (DN) is one of the complications with the highest mortality among diabetes patients and can lead to renal failure. Modified Huangfeng decoction (MHD) has been widely applied in the clinical treatment of kidney diseases. However, the mechanism by which MHD affects DN has not been fully elucidated.</div></div><div><h3>Purpose</h3><div>To investigate the impact of MHD on DN in mice and the underlying mechanism.</div></div><div><h3>Methods</h3><div>The main ingredients of MHD were identified by liquid chromatography‒mass spectrometry. A high-fat diet- and streptozotocin (STZ)-induced DN mouse model was constructed and treated with MHD for 6 weeks. The serum and urine parameters were measured, and the tissue sections were histologically stained. The mRNA and protein levels of metabolism-, inflammation-, fibrosis-, and autophagy-related markers were examined by qPCR and western blotting. The microbial composition and metabolites of cecal contents were analyzed through full-length 16S rRNA sequencing and nontargeted metabolomics.</div></div><div><h3>Results</h3><div>MHD alleviated insulin resistance in DN mice and ameliorated changes in lipid metabolism and inflammation in the liver and fat. In addition, MHD reduced the levels of kidney injury markers in the serum and urine and attenuated inflammation and fibrosis in the kidney. These results were accompanied by enhanced gut barrier function and a markedly altered microbiota composition and metabolites, with an increased abundance of beneficial bacterial species and metabolites. Moreover, MHD itself and the microbial metabolite spermidine reduced podocyte damage by activating autophagy via the PI3K/AKT/mTOR pathway.</div></div><div><h3>Conclusions</h3><div>MHD potentially ameliorated DN by activating podocyte autophagy via the PI3K/AKT/mTOR pathway and modulating the gut microbiota and its metabolites. Our findings provide a more comprehensive understanding of the mechanism of MHD and the involvement of the gut‒kidney interaction in the progression of DN, laying a theoretical foundation for the clinical application of MHD in DN treatment.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"141 ","pages":"Article 156677"},"PeriodicalIF":6.7,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143683115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated network pharmacology and experimental validation to elucidate the mechanism of celastrol in mitigating sepsis-induced acute lung injury in mice","authors":"Danli Zhu ,&nbsp;Jinghan Zhang ,&nbsp;Xiaochun Huang ,&nbsp;Na Wei ,&nbsp;Jinxiu Jiang ,&nbsp;Jiayao Li ,&nbsp;Li Liu ,&nbsp;Yulin Liu ,&nbsp;Jun Zhou ,&nbsp;Jing Jia","doi":"10.1016/j.phymed.2025.156678","DOIUrl":"10.1016/j.phymed.2025.156678","url":null,"abstract":"<div><h3>Background</h3><div>Sepsis is an acute, life-threatening condition that precipitates multiple organ failure, including acute lung injury (ALI), characterized by a complex pathophysiological process and elevated mortality rates. Celastrol, a pentacyclic triterpenoid quinone derived from traditional Chinese medicine, exhibits diverse pharmacological properties, including immunomodulatory, anti-inflammatory, anticancer, and antifibrotic effects, and has demonstrated favorable safety profiles in vivo. However, the precise mechanism by which CSL contributes to sepsis-induced ALI remains to be elucidated.</div></div><div><h3>Purpose</h3><div>The study aimed to explore the mechanisms by which celastrol mitigates sepsis-induced ALI using network pharmacology, followed by experimental validation of its regulatory effects on sepsis-induced ALI.</div></div><div><h3>Methods</h3><div>Utilizing a network pharmacology analysis, the potential targets and pathways of celastrol were identified. To explore celastrol's therapeutic effects on ALI, a rat model of sepsis was induced via cecal ligation and puncture, followed by assessment through hematoxylin-eosin staining, Real-time quantitative polymerase chain reaction (RT-qPCR), and Western blotting. Further investigation involved evaluating celastrol's influence on LPS-stimulated A549 and Raw264.7 cells, employing RT-qPCR, Western blotting, and immunofluorescence techniques.</div></div><div><h3>Results</h3><div>Network pharmacological analysis identified 10 core targets and 31 pathways relevant to sepsis-induced ALI, with STAT3, TLR4, HIF-1α, and NF-κB1 emerging as central targets. Animal experiments demonstrated that celastrol treatment significantly reduced lung tissue inflammation, as evidenced by immunohistochemistry, Western blot, and RT-qPCR results, in comparison to the cecal ligation and puncture group. Notably, the levels of IL-1β, TNF-α, HIF-1α, STAT3, and NF-κB1 proteins and mRNA in the celastrol treatment group were significantly reduced compared to those in the cecal ligation and puncture (CLP) group and the LPS-treated group. Additionally, Western blot and immunofluorescence analyses confirmed the activation of the NF-κB pathway in vitro.</div></div><div><h3>Conclusion</h3><div>This study indicates that celastrol significantly suppresses the expression of inflammatory factors in sepsis-induced ALI by inhibiting the NF-κB/HIF-1α pathway in both in vivo and in vitro models, highlighting its therapeutic potential for modulating inflammation. These findings provide valuable evidence for future clinical research and drug development.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"141 ","pages":"Article 156678"},"PeriodicalIF":6.7,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143683112","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Luteolin inhibits inflammation and M1 macrophage polarization in the treatment of Pseudomonas aeruginosa-induced acute pneumonia through suppressing EGFR/PI3K/AKT/NF-κB and EGFR/ERK/AP-1 signaling pathways","authors":"Mengdi Gu,&nbsp;Zheng Pang","doi":"10.1016/j.phymed.2025.156663","DOIUrl":"10.1016/j.phymed.2025.156663","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;The opportunistic pathogen &lt;em&gt;Pseudomonas aeruginosa&lt;/em&gt; primarily causes infections in immunocompromised individuals. Luteolin, a natural flavonoid, is widely present in plants, which exerts various pharmacological activities, including anti-inflammatory and antimicrobial activities.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Purpose&lt;/h3&gt;&lt;div&gt;This study aimed to explore the therapeutic efficacy of luteolin and the underlying molecular mechanisms in treating the &lt;em&gt;P. aeruginosa&lt;/em&gt;-induced acute pneumonia.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;Network pharmacology was utilized to identify the core targets of luteolin for treating acute &lt;em&gt;P. aeruginosa&lt;/em&gt; pneumonia. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed to dissect the potential effects of luteolin and the involved signaling pathways. Surface plasmon resonance (SPR) assay and molecular docking were employed for studying the binding affinities of luteolin with the key targets. Furthermore, we applied a mouse model of bacterial pneumonia for assessing the therapeutic effects of luteolin &lt;em&gt;in vivo&lt;/em&gt;, and an &lt;em&gt;in vitro&lt;/em&gt; infection model for specifically investigating the effects of luteolin on macrophages as well as the underlying mechanisms upon &lt;em&gt;P. aeruginosa&lt;/em&gt; infection.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Network pharmacology identified TNF, IL-6, EGFR and AKT1 as the key targets of luteolin for treating acute &lt;em&gt;P. aeruginosa&lt;/em&gt; pneumonia. Moreover, as revealed by GO and KEGG enrichment analysis, EGFR, MAPK and PI3K/AKT pathways were the potential pathways regulated the &lt;em&gt;P. aeruginosa&lt;/em&gt;-induced inflammatory response. According to the &lt;em&gt;in vivo&lt;/em&gt; results, luteolin effectively mitigated the &lt;em&gt;P. aeruginosa&lt;/em&gt;-induced acute lung injury through reducing the pulmonary permeability, neutrophil infiltration, proinflammatory cytokine production (IL-1β, IL-6, TNF and MIP-2) and bacterial burden in lung tissues, which led to increased survival rate of mice. Furthermore, the luteolin-treated mice had diminished EGFR, PI3K, AKT, IκBα, NF-κB p65, ERK, c-Jun and c-Fos phosphorylation, down-regulated M1 macrophage marker levels (iNOS, CD86 and IL-1β) but up-regulated M2 macrophage marker levels (Ym1, CD206 and Arg1) in lung tissues. Consistently, the luteolin-pretreated macrophages exhibited reduced phosphorylation of these regulatory proteins, diminished proinflammatory cytokine production, and down-regulated expression of M1 macrophage markers, but up-regulated expression of IL-10 and M2 macrophage markers.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;luteolin effectively suppressed the inflammatory responses and M1 macrophage polarization through inhibiting EGFR/PI3K/AKT/NF-κB and EGFR/ERK/AP-1 signaling pathways in the treatment of acute &lt;em&gt;P. aeruginosa&lt;/em&gt; pneumonia. This study suggests that luteolin could be a promising candidate for development as a therapeutic agent for acute bacterial pneumo","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"141 ","pages":"Article 156663"},"PeriodicalIF":6.7,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143683113","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to \"Notoginsenoside R1 alleviates cerebral ischemia/reperfusion injury by inhibiting the TLR4/MyD88/NF-κB signaling pathway through microbiota-gut-brain axis\" [Phytomedicine 128 (2024) 155530].","authors":"Shuxia Zhang, Qiuyan Chen, Meiqi Jin, Jiahui Ren, Xiao Sun, Zhixiu Zhang, Yun Luo, Xiaobo Sun","doi":"10.1016/j.phymed.2025.156635","DOIUrl":"https://doi.org/10.1016/j.phymed.2025.156635","url":null,"abstract":"","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":" ","pages":"156635"},"PeriodicalIF":6.7,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143670826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ginkgo biloba Extract GBE50 ameliorates cerebrovascular dysfunction and cognitive impairment in a mouse model of Alzheimer's disease","authors":"Ting Yu ,&nbsp;Zijie Wei ,&nbsp;Jing Wang ,&nbsp;Chenghuan Song ,&nbsp;Wanying Huang ,&nbsp;Pingao Zhang ,&nbsp;Jiyun Shi ,&nbsp;Rui Zhang ,&nbsp;Meifang Jiang ,&nbsp;Dandan Wang ,&nbsp;Yongfang Zhang ,&nbsp;Hongzhuan Chen ,&nbsp;Hao Wang","doi":"10.1016/j.phymed.2025.156646","DOIUrl":"10.1016/j.phymed.2025.156646","url":null,"abstract":"<div><h3>Background</h3><div>Alzheimer's disease (AD) is a complex neurodegenerative disorder in which neurovascular unit (NVU) dysfunction plays a critical role. GBE50, a refined extract of <em>Ginkgo biloba</em> containing over 50 % total flavonoids and terpene lactones, is widely used in the clinical prevention and treatment of cardiovascular and cerebrovascular diseases due to its anti-platelet aggregation, anti-inflammatory, and antioxidant properties. However, its specific effects on NVU integrity and cerebrovascular function in AD remain unclear.</div></div><div><h3>Purpose</h3><div>This study aims to investigate the therapeutic effects of GBE50 on NVU integrity and cognitive impairment in an AD mouse model.</div></div><div><h3>Methods</h3><div>APP/PS1 transgenic mice were treated with GBE50 <em>via</em> intragastric administration for 10 weeks. Cognitive performance was assessed through behavioral tests, while the structural and functional integrity of the NVU was evaluated using immunofluorescence, laser speckle imaging, and <em>in vivo</em> multi-photon imaging. Furthermore, target prediction and transcriptomic analyses were conducted to uncover potential molecular mechanisms and identify specific targets of GBE50.</div></div><div><h3>Results</h3><div>GBE50 treatment significantly alleviated cognitive deficits in APP/PS1 mice. It enhanced cerebrovascular structure and function by increasing vessel density, diameter, and branching, leading to improved cerebral blood flow (CBF). GBE50 also restored NVU components such as endothelial cells, astrocytes, and pericytes, promoted parenchyma and perivascular Aβ clearance, and reduced neuroinflammation. Bioinformatics and transcriptomic analyses revealed that GBE50 exerted its effects by regulating pathways related to vascular repair, neuroprotection, and Aβ clearance.</div></div><div><h3>Conclusion</h3><div>The findings demonstrate that GBE50 improves cognitive dysfunction in AD by restoring NVU integrity and cerebrovascular function through multi-target mechanisms. This study highlights the potential of GBE50 as a promising therapeutic approach for AD and other neurodegenerative diseases involved in cerebrovascular dysfunction.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"141 ","pages":"Article 156646"},"PeriodicalIF":6.7,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143697733","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The pathogenesis of hepatocellular carcinoma: ERK/ULK1/NCOA4-mediated inhibition of iron autophagy, and Epimedium extract targeted modulation of this pathway to treat hepatocellular carcinoma","authors":"Liying Han ,&nbsp;Xiangmu Tian ,&nbsp;Xinxin Yang ,&nbsp;Tianjiao Li ,&nbsp;Shuai Wang ,&nbsp;Yongrui Bao ,&nbsp;Xiansheng Meng","doi":"10.1016/j.phymed.2025.156666","DOIUrl":"10.1016/j.phymed.2025.156666","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;The pathogenesis of hepatocellular carcinoma (HCC) is characterized by its complexity and diversity, involving processes such as glycolysis, autophagy, and cellular immunity. Notably, the role of ERK/ULK1/NCOA4-mediated inhibition of iron autophagy in HCC pathogenesis has not been previously reported. This study provides a novel elucidation of HCC pathogenesis and identifies the clinical adjuvant therapy drug, Epimedium, as a potential treatment based on this mechanism. The research clarifies the regulatory effects of Epimedium on the ERK/ULK1/NCOA4-mediated inhibition of iron autophagy pathway in the treatment of HCC, thereby offering a scientific foundation for clinical treatment strategies and the development of innovative drugs.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Purpose&lt;/h3&gt;&lt;div&gt;The objective of this study is to uncover a new aspect of HCC pathogenesis, ERK/ULK1/NCOA4-mediated inhibition of iron autophagy, and to screen for clinical targeted adjuvant therapy drugs based on this mechanism.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;A HCC rat model was induced with N-Nitrosodiethylamine (DEN). The physiological status of the HCC rats was assessed through indicators such as body weight and organ index. Liver damage in HCC rats was evaluated using hematoxylin and eosin (HE) staining and biochemical markers. Additionally, untargeted metabolomics was employed to explore the pathogenesis of HCC. UPLC-Q-TOF-MS combined with network pharmacology was employed to elucidate novel mechanisms, predict pathway targets, filtrate active ingredients and analyze the biological processes and signaling pathways modulated by EPME. DEN liver cancer rats were treated with different concentrations of EPME and protein expression levels were assessed by Western blot analysis. Molecular docking techniques were utilized to assess the binding affinity between the core components of EPME and target proteins. A HepG2 liver cancer in vitro model, in combination with inhibitor (SBI-0206965), was employed to verify the modulatory effects of EPME and its active ingredients on the ERK/ULK1/NCOA4 signaling pathway. Microscale thermophoretic (MST) was employed to verify the binding ability of the EPME core components to the ULK1 protein.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Metabolomics combined with network pharmacology revealed a novel pathogenesis of HCC, which is ERK/ULK1/NCOA4-mediated iron autophagy inhibition. EPME can activate iron autophagy mediated by ERK/ULK1/NCOA4 through active ingredients such as icaritin, astragalin, and emodin, thereby enhancing the survival conditions of HCC-afflicted rats and mitigating liver damage and carcinogenesis, ultimately achieving therapeutic outcomes in HCC treatment.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;The ERK/ULK1/NCOA4-mediated iron autophagy inhibition represents a novel therapeutic mechanism for HCC. The clinical adjuvant drug EPME may exert therapeutic effects on HCC by activating ERK/ULK1/NCOA4-mediated iron autophag","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"141 ","pages":"Article 156666"},"PeriodicalIF":6.7,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143683110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting neutrophil dysfunction in acute lung injury: Insights from active components of Chinese medicine","authors":"Saiya Ye ,&nbsp;Lin Ma ,&nbsp;Yannan Chi ,&nbsp;Ning Liu ,&nbsp;Yue Liu ,&nbsp;Wei Wei ,&nbsp;Yang Niu ,&nbsp;Ping Zheng ,&nbsp;Jianqiang Yu ,&nbsp;Dongmei Hai","doi":"10.1016/j.phymed.2025.156664","DOIUrl":"10.1016/j.phymed.2025.156664","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Backgrounds&lt;/h3&gt;&lt;div&gt;Acute lung injury (ALI) is a lethal condition characterized by uncontrolled pulmonary inflammatory responses, with high morbidity and mortality rates that pose a significant threat to patient health. The persistent retention of neutrophils in lung tissue and subsequent inflammatory damage represents a primary mechanism underlying the early onset of ALI disorders. In recent years, pharmaceutical research targeting these pathological processes has garnered considerable attention. Traditional Chinese medicines (TCM) and their active ingredients, known for their safety and stability, show promising potential in treating ALI through their ability to modulate neutrophil function via multiple pathways.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Purpose&lt;/h3&gt;&lt;div&gt;This review examines the mechanisms of neutrophil involvement in the pathogenesis of ALI, investigates potential therapeutic targets and pathways through which Chinese medicines and their active ingredients regulate neutrophil function, and provides a theoretical foundation for developing novel clinical treatment strategies.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;A comprehensive literature search was conducted using multiple databases, including Science Direct, PubMed, Google Scholar, and Web of Science. Search terms included 'lung injury,' 'acute lung injury,' 'inflammatory lung injury,' 'inflammation,' 'active ingredient,' 'herbal,' 'traditional Chinese medicine,' 'mechanism,' 'drug,' and 'neutrophils.' The selected literature was systematically categorized and analyzed.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Our review reveals that TCM and active ingredients influence neutrophil function through four primary mechanisms to impede ALI progression: 1) reduction of neutrophil-mediated uncontrolled inflammatory responses by suppressing neutrophil hyperactivation and inhibiting neutrophil migration and infiltration; 2) attenuation of lung tissue inflammatory damage by inhibiting neutrophil-produced cytotoxic substances, including elastase granules, neutrophil extracellular traps (NETs), and reactive oxygen species (ROS); 3) suppression of inflammatory responses by decreasing the secretion of neutrophil-derived cytokines, such as interleukin (IL) -1β, IL-6 and tumor necrosis factor-alpha (TNF-α); and 4) enhancement of neutrophil phagocytosis and accelerate the removal of apoptotic neutrophils to eliminate harmful pathogens and promote late-stage tissue repair. These findings demonstrate that Chinese medicines and their active ingredients exhibit significant therapeutic potential in ALI disorders through the modulation of neutrophil function, providing a robust theoretical framework for their clinical applications.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;Traditional Chinese medicines and their active ingredients demonstrate significant anti-inflammatory efficacy through multiple mechanisms of neutrophil function regulation, showing considerable promise for the treatment of ALI with broad clinical a","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"141 ","pages":"Article 156664"},"PeriodicalIF":6.7,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143683109","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}